Selective modification of macromolecules is desirable to tailor their structural and functional properties, such as hydrophobicity, hydrophilicity, and interfacial and film forming properties. E.g., fatty acid esters of macromolecules may be useful as bioerodable and biodegradable drug delivery matrices such as coatings, finishes and films, and biodegradable emulsifiers, compatibilizers and detergents.1 However, selective acylation of hydroxylated macromolecules by chemical reactions are difficult due to multiple steps involved in the modification (protection, deprotection, extraction, separation and purification), and due to the lack of specificity, solubility and the presence of multifunctional groups in the polymer.2 Enzymes have been used to acylate saccharides of different glucose moieties regioselectively under mild condition in organic solvents. 2-4 Similar reactions with other hydroxylated macromolecules would be desirable. However, the lack of solubility of these polymers and the enzymes in organic solvents implies significant problems in carrying out these conversions. Accordingly, alternate methods of achieving a functionally significant degree of modifications are required. 5-7
Enzymes are powerful catalysts in organic solvents where they catalyze a wide variety of reactions that are difficult to perform in aqueous solutions. This is particularly evident in esterification reactions catalyzed by lipases and proteases wherein a variety of nucleophiles act as substrates for enzyme-catalyzed acyl transfer in nearly anhydrous organic solvents. Unfortunately, many hydroxylated compounds are either sparingly soluble in only the most polar organic solvents, or are completely insoluble in organic media. For these substrates, conventional non-aqueous enzymology is unable to support catalytic transformations. The development of a suitable technique for the selective modification of macromolecules in organic solvents, therefore, would represent both an opportunity for the synthesis of novel materials as well as means to overcome a technical hurdle in the broader uses of enzymes in non-aqueous media.
Accordingly, it is an object of this invention to overcome the above illustrated inadequacies and problems of insoluble macromolecules by providing a improved method of their modification.
It is another object of this invention to provide a method of acylating hydroxylated macromolecules wherein their selective modification results in structural and/or functional benefits.
Yet another object of the present invention is to provide a method of enabling the use of enzymes to catalyze reactions in non-aqueous media for the synthesis of biodegradable, bioerodable and biocompatible compounds.